Minimally invasive methods for locating an optimal location for deep brain stimulation

ABSTRACT

Methods of locating an optimal site within a brain of a patient for deep brain stimulation include positioning a guiding cannula in a lumen of a main cannula, passing a microelectrode through a lumen of the guiding cannula into the brain, adjusting an insertion depth and a longitudinal angle of the guiding cannula such that the microelectrode locates the optimal site for the deep brain stimulation, and passing a distal end of a macroelectrode or a deep brain stimulation lead through the lumen of the main cannula and into the brain at the optimal site.

BACKGROUND

Deep brain stimulation (DBS) and other related procedures involving theimplantation of leads and catheters in the brain are increasingly usedto treat such conditions as Parkinson's disease, dystonia, essentialtremor, seizure disorders, obesity, depression, motor control disorders,and other debilitating diseases. During these procedures, a catheter,lead, or other medical device is strategically placed at a target sitein the brain. Locating the “best” or optimal site in the brain for deepbrain stimulation can be a painstaking procedure.

Implantation of a lead for DBS generally involves the followingpreliminary steps: (a) anatomical mapping and (b) physiological mapping.Anatomical mapping involves mapping segments of an individual's brainanatomy using non-invasive imaging techniques, such as magneticresonance imaging (MRI) and computed axial tomography (CAT) scans.Physiological mapping involves locating the brain site to be stimulated.Step (b) can be further divided into: (i) preliminarily identifying apromising brain site by recording individual cell activity with amicroelectrode and (ii) confirming physiological stimulation efficacy ofthat site by performing a test stimulation with a macroelectrode ormicroelectrode.

Microelectrode recording is generally performed with a microelectroderecording (MER) system. The MER system includes a small diameterelectrode with a relatively small surface area optimal for recordingsingle cell activity. The microelectrode may essentially be an insulatedwire that has at least the distal portion uninsulated to receiveelectrical signals. The microelectrode functions as a probe to locate anoptimal site in the brain for deep brain stimulation. Activity detectedthrough the microelectrode is recorded by the MER system. Since a numberof attempts may be required to locate the optimal site, it is desirablethat the microelectrode be as small as possible to minimize trauma whenthe microelectrode is introduced into the brain, in some cases, multipletimes.

Once an optimal site in the brain for deep brain stimulation has beenidentified by the microelectrode recording, a macroelectrode is used totest whether the applied stimulation has the intended therapeuticeffect. Once macrostimulation confirms that stimulation at the optimalsite provides the intended therapeutic effect, the macroelectrode iswithdrawn from the brain and a DBS lead is permanently implanted at theoptimal site in the brain for deep brain stimulation.

There are a number of commercially available MER systems used in deepbrain stimulation. One exemplary MER system permits the neurosurgeon tosimultaneously record an output from five different microelectrodes,referred to as “five-at-a-time.” In this approach, five microelectrodesare advanced into the brain at the same time and at the same speed. Thispresents obvious advantages. The set-up time may be proportionately cut,since the chance of locating an optimal stimulation site theoreticallyincreases by five fold. However, the size and configuration of thissystem is more likely to cause damage to brain tissue. For instance,because the microelectrodes in a “five-at-a-time” system are placedrelatively close to each other, two of these electrodes may sometimes“capture” a blood vessel between them. This may result in vesselpunctures and may lead to intracranial bleeding. In contrast, when asingle microelectrode is used, a blood vessel can often escape injurybecause the vessel can deflect away from the microelectrode, orvice-versa. Thus, some neurosurgeons choose to use an MER system withonly a single microdrive, advancing one microelectrode at a time untilan optimal stimulation site is found.

The recorded output of a microelectrode advanced along a path throughthe brain is referred to as a recording tract. Some neurosurgeonsaverage four to five microelectrode recording tracts before they decideon an optimal site in the brain for deep brain stimulation. Otherneurosurgeons only use one recording tract, which cuts surgery duration,but which may not locate the optimal stimulation site. Without optimalelectrode placement, the DBS lead may need to be driven at a highercurrent to produce the desired therapeutic effect. This, however, cancause the device battery to be drained more quickly. In addition, theuse of higher currents can increase the risk of undesirable side effectssuch as dysarthria (slurred speech) and abulia (an abnormal inability tomake decisions or to act).

Each of these MER systems applies the conventional surgical procedure ofcreating multiple microelectrode tracts until an optimal site for deepbrain stimulation is found within the brain. On average, a singlemicroelectrode recording tract takes approximately thirty minutes toperform. Each microelectrode recording tract requires placement of themicroelectrode via a larger diameter insertion cannula through viablebrain tissue. Each time an object is inserted into the brain there isapproximately a five percent risk of hemorrhage. Creating multipletracts increases the risk for intracranial bleeding, duration ofoperation, post-operative infection, and operative risk. Creating newtracts is fraught with misalignment/misplacement problems because theintroduction cannulas may not always trace the exact pathways desired.

SUMMARY

Methods of locating an optimal site within a brain of a patient for deepbrain stimulation include positioning a guiding cannula in a lumen of amain cannula, passing a microelectrode through a lumen of the guidingcannula into the brain, adjusting an insertion depth and a longitudinalangle of the guiding cannula such that the microelectrode locates theoptimal site for the deep brain stimulation, and passing a distal end ofa macroelectrode or a deep brain stimulation lead through the lumen ofthe main cannula and into the brain at the optimal site.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate various embodiments of the presentinvention and are a part of the specification. The illustratedembodiments are merely examples of the present invention and do notlimit the scope of the invention.

FIG. 1 shows a schematic diagram of an exemplary deep brain stimulation(DBS) lead insertion system according to principles described herein.

FIG. 2 illustrates an exemplary guiding cannula according to principlesdescribed herein.

FIGS. 3A-3B show that the precise location of the microelectrode tip maybe calculated using a number of mathematical formulas according toprinciples described herein.

FIG. 4A is a side view of an exemplary depth adjustment mechanismaccording to principles described herein.

FIG. 4B is a half cross-sectional view of the depth adjustment mechanismtaken along the perspective line indicated in FIG. 4A according toprinciples described herein.

FIG. 4C is a top view of the depth adjustment mechanism of FIG. 4Aaccording to principles described herein.

FIG. 5A is a cross sectional side view of the main base according toprinciples described herein.

FIG. 5B is a top view of the main base taken along the perspective lineindicated in FIG. 5A according to principles described herein.

FIG. 6A is a top view of an exemplary guiding plate according toprinciples described herein.

FIG. 6B is a cross-sectional side view of the guiding plate taken alongthe perspective line of FIG. 6A according to principles describedherein.

FIG. 7 illustrates an exemplary retaining rail according to principlesdescribed herein.

FIG. 8 is a top view of an exemplary longitude adjustment plateaccording to principles described herein.

FIG. 9 is a flow chart illustration an exemplary method of locating anoptimal site within the brain of a patient for deep brain stimulationaccording to principles described herein.

FIGS. 10A-10G illustrate various steps in an exemplary method oflocating an optimal site within the brain of a patient for deep brainstimulation according to principles described herein.

Throughout the drawings, identical reference numbers designate similar,but not necessarily identical, elements.

DETAILED DESCRIPTION

The present application is related to an application entitled “MinimallyInvasive Systems for Locating an Optimal Location for Deep BrainStimulation” to Malinowski et al., client docket number AB-333U1, whichapplication is to be filed on the same day as the present application.The AB-333U1 application is incorporated herein by reference in itsentirety.

Minimally invasive methods and systems for making a preciseidentification of an optimal site within the brain of a patient for deepbrain stimulation (DBS) are described herein. A main cannula is firstcoupled to a stereotactic instrument, which is configured to mount onthe head of a patient. The main cannula has a distal end that isinserted into the brain. A guiding cannula is then passed through alumen of the main cannula and inserted further into the brain startingat an initial insertion depth determined by the insertion depth of themain cannula. A microelectrode may then be passed through the guidingcannula and positioned within the brain. The insertion depth and/orlongitudinal angle of the guiding cannula may be adjusted with a depthadjustment mechanism and/or a longitudinal angle adjustment device,respectively, such that the microelectrode locates the optimal site forthe deep brain stimulation. Once the microelectrode locates the optimalsite for deep brain stimulation, the exact coordinates of the optimalsite for deep brain stimulation are calculated. These coordinates maythen be used to subsequently insert a macroelectrode or deep brainstimulation lead within the brain and provide macrostimulation and/ordeep brain stimulation at the optimal site for deep brain stimulation.

In the following description, for purposes of explanation, numerousspecific details are set forth in order to provide a thoroughunderstanding of the present systems and methods. It will be apparent,however, to one skilled in the art that the present systems and methodsmay be practiced without these specific details. Reference in thespecification to “one embodiment” or “an embodiment” means that aparticular feature, structure, or characteristic described in connectionwith the embodiment is included in at least one embodiment. Theappearance of the phrase “in one embodiment” in various places in thespecification are not necessarily all referring to the same embodiment.

The term “deep brain stimulation” or “DBS” will be used herein and inthe appended claims, unless otherwise specifically denoted, to refer toany therapeutic stimulation that may be applied to any stimulation sitewithin the brain of a patient. The deep brain stimulation may includeelectrical stimulation and/or drug stimulation.

FIG. 1 shows a schematic diagram of an exemplary deep brain stimulation(DBS) lead insertion system (100). The DBS lead insertion system (100)may include a number of components. The example shown in FIG. 1 ismerely illustrative and components may be removed, added to, or replacedas best serves a particular DBS application. The components of the DBSlead insertion system (100) may be made out of any suitable material(s)as best serves a particular DBS application. For example, some or all ofthe components of the DBS lead insertion system (100) may be made out ofstainless steel or other biocompatible materials such as titanium alloy.

The exemplary DBS lead insertion system (100) of FIG. 1 includes a mainbase (101) configured to support a number of additional components ofthe DBS lead insertion system (100) as will be described below. The mainbase (101) is coupled to a stereotactic frame (109) using a mountingstructure (191). The stereotactic frame (109) holds the components ofthe DBS lead insertion system (100) during a DBS procedure. FIG. 1 alsoshows a skull (115), dura mater (116), and brain (117) of a patient.

As shown in FIG. 1, a main cannula (102) is inserted into the brain(117) and is configured to allow passage of a guiding cannula (103),sometimes called a microstimulator-guiding cannula, into the brain(117). The guiding cannula (103), in turn, is configured to allowpassage of a microelectrode (110) into the brain (117). Themicroelectrode (110) may be used to perform microelectrode recording orprobing of individual cell activity to locate an optimal site within thebrain (117) for deep brain stimulation. A macroelectrode and/or a DBSlead may subsequently be inserted into the brain (117) at the optimalsite via the main cannula (102) to provide test stimulation(macrostimulation) and/or deep brain stimulation, as will be explainedin more detail below. The DBS lead may be a lead having a number ofelectrodes for electrical stimulation of the brain. The DBS lead mayalternatively be a catheter for providing drug stimulation to the brain.Hence, as used herein and in the appended claims, unless otherwisespecifically denoted, the term “DBS lead” will be used to refer to anylead having a number of electrodes or to a catheter.

The DBS lead insertion system (100) may further include a depthadjustment mechanism (104) for adjusting the depth of the guidingcannula (103) within the brain (117) and a longitude adjustment plate(105) for adjusting the longitudinal position of the guiding cannula(103) within the brain (117). A longitudinal locking mechanism (106),which may be a longitudinal locking nut, locks the microelectrode (110)in a particular longitudinal position. A guiding plate (107) and aretaining rail (108) may also be provided to maintain a preciselongitudinal direction of the guiding cannula (103). Each of thecomponents of the DBS lead insertion system (100) shown in FIG. 1 willbe explained in more detail below.

FIG. 2 illustrates an exemplary guiding cannula (103). The guidingcannula (103) may be prefabricated and made from a Nitinol alloy or anyother suitable material configured to retain its shape even aftertemporary or accidental deformation. Nitinol alloys are known for theirsuperelasticity and shape memory properties. Nitinol alloys maytherefore be configured to have an optimum superelastic behavior at bodytemperature.

As shown in FIG. 2, the guiding cannula (103) has a cylindrical tubularform. A proximal end portion (121) of the guiding cannula (103) may beconfigured to couple to the guiding plate (107; FIG. 1) of the leadinsertion system (100; FIG. 1) described above. The proximal end portion(121) may also include, for example, a permanently fixed flange (124).

The guiding cannula (103) may also include a bent distal end portion(120) with a known radius (r). The bent distal end portion (120)includes a distal tip (123), as shown in FIG. 2. When the distal tip(123) of the guiding cannula (103) exits from the main cannula (102;FIG. 1), the distal tip (123) of the guiding cannula (103) follows thecircumferential predetermined tract of the guiding cannula's distal endbend portion (120), which has a predetermined radius (r). In somealternative embodiments, the distal end portion (120) is straight.

As shown in FIG. 2, a microelectrode (110) may be inserted within theguiding cannula (103) with a distal tip (122) of the microelectrode(110) extending from the bent distal end portion (120) of the guidingcannula (103). The microelectrode (110) has an uninsulated tip (122)with a relatively small surface area configured to probe different areasof the brain and record or probe single cell activity. The remainingportions of the microelectrode (110) may be protected with an insulativematerial such as, but not limited to, a Teflon® coat and/or housedwithin a carrier protective tube made out of an insulative material suchas, but not limited, to stainless steel.

As will be described in more detail below, the insertion depth withinthe brain of the distal tip (123) of the guiding cannula (103) may beadjusted with the depth adjustment mechanism (104; FIG. 1) mentionedabove. The guiding cannula (103) may also be rotated about a verticalaxis of the main cannula (102; FIG. 1) using the longitude adjustmentplate (105; FIG. 1) such that 3-dimensional probing of the brain withthe microelectrode (110) may be accomplished. Hence, an optimal sitewithin the brain for deep brain stimulation may be precisely establishedby probing multiple points within the 3-dimensional range of themicroelectrode (110).

FIGS. 3A-3B show that the precise location of the microelectrode tip maybe calculated using a number of mathematical formulas. FIG. 3A is a sideview of the main cannula (102), the guiding cannula (103), and themicroelectrode (110) and shows the depth, or vertical position, of thedistal tip (123) of the guiding cannula (103) and the microelectrode tip(122). FIG. 3B is a top view of the main cannula (102), the guidingcannula (103), and the microelectrode (110) and shows the longitudinalposition of the distal tip (123) of the guiding cannula (103) and themicroelectrode tip (122).

In the following formulas, it is assumed that the coordinate of thedistal end (130) of the main cannula (102) is 0,0,0. Table 1, shownbelow, defines a number of variables that will be used in the followingformulas. TABLE 1 Variable Definitions Variable Definition h A maximumpossible insertion depth of the distal tip (123) of the guiding cannula(103). The length of h is equivalent to the arc length s (the dashedcenter line of the guiding cannula (103)). h + AB A maximum possibleinsertion depth of the tip (122) of the microelectrode (110). h′ Theactual insertion depth of the distal tip (123) of the guiding cannula(103). h′ + AB · cosα The actual insertion distance of the tip (122) ofthe microelectrode (110). θ The longitudinal angle, defined as an anglefrom an established direction at 0 degrees. α The exit angle for themicroelectrode (110). A_((x′,y′,z′)) The actual location of the distaltip (123) of the guiding cannula (103). The location has threedimensional components equal to x′, y′, and z′. B_((x,y,z)) The actuallocation of the distal tip (122) of the microelectrode (110). Thelocation has three dimensional components equal to x, y, and z.

The point labeled “A” in FIGS. 3A and 3B represents the location of thecenter of the distal tip (123) of the guiding cannula (103) and thepoint labeled “B” represents the location of the microelectrode tip(122). Point B may alternatively represent the location of the distaltip of a macroelectrode and/or a DBS lead that is inserted into the maincannula (102). Calculation of the coordinates for point A may includethe following sequence of equations:α=360h/πr ²  Equation 1h′=r·sin α=r·sin(360h/πr ²)  Equation 2a′=r·(1−cos α)=r·(1−cos(360h/πr ²));  Equation 3x′=a′·cos θ;  Equation 4y′=a′·sin θ; and  Equation 5zζ=hζ=r·sin(360h/π ²)  Equation 6

Therefore, the coordinates of A may be defined asA _((x′, y′, z′)) =A _((a′·cos θ,a′·sin θ,r·sin(360h/πr) ₂ ₎₎.

Likewise, calculation of the coordinates for point B may include thefollowing sequence of equations:a=a′+AB·sin α=r·(1−cos(360h/πr ²))+AB·sin(360h/π ²);  Equation 1x=a·cos θ;  Equation 2y=a·sin θ; and  Equation 3z=h′+AB·cos(360h/πr ²)=r·sin(360h/πr ²)+AB·cos(360h/πr ²).  Equation 4

Therefore, the coordinates of B may be defined asB _((x,y,z)) =B _((a·cos θ,a·sin θ,r·sin(360h/πr) ₂ _()+AB·cos(360h/πr)₂ ₎₎.

The equations listed above may be modified to suit a particularcoordinate system. Moreover, the equations listed above are merelyexemplary of a set of equations that may be used to calculate thecoordinates of the locations of the distal tip (123) of the guidingcannula (103) and the microelectrode tip (122). In some embodiments, theequations listed above, or an alternative set of equations, may beimplemented and/or calculated using a computing device or computerprogram to acquire the precise coordinates of points A and B. Thecomputing device and/or computer program may be used in conjunction withthe depth adjustment mechanism (104; FIG. 1) and/or the longitudeadjustment plate (105; FIG. 1) to automatically calculate the precisecoordinates of the distal tip (123) of the guiding cannula (103) and themicroelectrode tip (122). The calculated coordinates may then be used toposition a macroelectrode and/or DBS lead in the brain at the optimalsite within the brain for deep brain stimulation as determined by theprobing performed by the microelectrode (110).

As mentioned, the insertion depth of the guiding cannula (103) withinthe brain may be adjusted with the depth adjustment mechanism (104; FIG.1). FIG. 4A is a side view of an exemplary depth adjustment mechanism(104) that may be used to make precision adjustments to the depth of theguiding cannula (103). FIG. 4B is a half cross-sectional view of thedepth adjustment mechanism (104) taken along the perspective lineindicated in FIG. 4A. FIG. 4C is a top view of the depth adjustmentmechanism (104) of FIG. 4A. As shown in FIGS. 4A and 4C, the depthadjustment mechanism (104) has a cylindrical form. FIG. 4B shows thatthe depth adjustment mechanism (104) has an internal thread (140). Theinternal thread (140) matches an external thread of the main base (101;FIG. 1), as described below in connection with FIGS. 5A and 5B. In someembodiments, the internal thread (140) is configured such that onecomplete revolution of the depth adjustment mechanism (104) equals achange in depth equal to one millimeter (mm). The change in depth perrevolution of the depth adjustment mechanism (104) may vary as bestserves a particular application.

As shown in FIG. 4A, the outer surface of the depth adjustment mechanism(104) may include a number of horizontal marks (145) for measuring aninsertion depth of the guiding cannula (103; FIG. 1). A number oflateral marks (146) may also be included on the outer surface of thedepth adjustment mechanism (104) for making very fine insertion depthadjustments and measurements. For example, ten evenly circumferentiallydistributed lateral marks (146) may be included on the outer surface ofthe depth adjustment mechanism (104). If one revolution of the depthadjustment mechanism (104) equals a change in depth equal to onemillimeter, the radial distance between two adjacent lateral marks (146)is equal to one tenth of one revolution. Hence, the insertion depth ofthe guiding cannula (103; FIG. 1) may be adjusted with a resolution of0.1 millimeters. It will be recognized that there may be any number ofevenly distributed lateral marks (146) on the outer surface of the depthadjustment mechanism (104) as best serves a particular application.

An opening (147) in the top of the depth adjustment mechanism (104), asshown FIG. 4C, allows for the guiding cannula (103; FIG. 1),microelectrode (110; FIG. 1), macroelectrode, and/or DBS lead to passthrough the lumen of the depth adjustment mechanism (104). The opening(147) may be rectangular in shape, as shown in FIG. 4C. However, it willbe recognized that the opening (147) may have any shape as best serves aparticular DBS lead insertion system (100; FIG. 1).

The depth adjustment mechanism (104) illustrated in connection withFIGS. 4A-4C is merely exemplary of any depth adjustment mechanism (104)that may be used to adjust and measure the depth of the guide cannula(103; FIG. 1) with a high degree of precision. Other configurations ofthe depth adjustment mechanism (104) may be used as best serves aparticular DBS application. For example, the depth adjustment mechanism(104) may additionally or alternatively include a computerized motor orthe like configured to adjust the insertion depth of the guiding cannula(103; FIG. 1).

FIGS. 5A and 5B illustrate an exemplary main base (101). FIG. 5A is across sectional side view of the main base (101) and FIG. 5B is a topview of the main base (101) taken along the perspective line indicatedin FIG. 5A. As shown in FIG. 5A, the main base (101) includes anexternal thread (150) which matches and couples to the internal thread(140; FIG. 4B) of the depth adjustment mechanism (104; FIG. 4A). Anopening (151) in the main base (101) allows the main cannula (102;FIG. 1) to pass through lumen of the main base (101) and extend into thebrain.

As shown in FIG. 5B, the main base (101) may include a cylindrical ring(155) with a number of marks (156) located on a top surface of the ring(155) indicating a range of possible longitudinal angles of the distaltip (123; FIG. 2) of the guiding cannula (103; FIG. 2). For example, asshown in FIG. 5B, the cylindrical ring (155) includes a number of marks(156) indicating a range of longitudinal angles between zero and 360degrees. The number of marks (156) indicating longitudinal angles mayvary as best serves a particular DBS lead insertion system (100; FIG.1). As will be described below, a notch on the longitude adjustmentplate (105; FIG. 1) may be aligned to match a desired longitudinal angleas indicated by the marks (156) on the top surface of the cylindricalring portion (155) of the main base (101).

FIG. 6A is a top view of an exemplary guiding plate (107). The guidingplate (107) includes an opening (160) which is used to couple theguiding plate (107) to the proximal end (121; FIG. 2) of the guidingcannula (103; FIG. 2). The opening (160) may have a rectangular shape,as shown in FIG. 6A, or any other shape as best serves a particular DBSlead insertion system (100; FIG. 1). The guiding plate (107) may becoupled to the retaining rail (108; FIG. 1) via a retaining lumen (161).As will be illustrated in more detail below, coupling the guiding plate(107) to the retaining rail (108; FIG. 1) ensures that the guidingcannula (103; FIG. 1) will be inserted into the brain at a desiredlongitudinal angle.

FIG. 6B is a cross-sectional side view of the guiding plate (107). FIG.6B shows that a guiding tube (162) or a sleeve may be inserted into theretaining lumen (161). The guiding tube (162) may be used to compensatefor differences in the dimensions of the retaining lumen (161) and theretaining rail (108; FIG. 1). The guiding tube (162) may be made out ofany suitable material. In some embodiments, the guiding tube (162) maybe made out of a plastic or material configured to conform to thedimensions of the retaining rail (108; FIG. 1). In some alternativeembodiments, the guiding plate (107) is coupled to the retaining rail(108; FIG. 1) without the use of the guiding tube (162).

FIG. 7 illustrates an exemplary retaining rail (108). The retaining rail(108) includes a straight pin (170) and a wing member (171). Thestraight pin (170) may be made out of any material having highdimensional and geometrical tolerances in order to maintain a preciselongitudinal angle for the guiding cannula (103; FIG. 1). For example,the straight pin (170) may be made out of stainless steel. The straightpin (170) has a circumference small enough such that straight pin (170)fits into the guiding tube (162; FIG. 6B) and/or the retaining lumen(161; FIG. 6B). In this manner, the straight pin (170) is used to couplethe retaining rail (108) to the guiding plate (107; FIG. 6A).

The wing member (171) of the retaining rail (108) may extend in adirection perpendicular to the axis of the straight pin (170), as shownin FIG. 7. The wing member (171) may include a horizontal reference mark(172) that may be used to initially position the depth adjustmentmechanism (104; FIG. 4A). The horizontal reference mark (172) is alsoused in connection with the horizontal marks (145; FIG. 4A) to measurethe insertion depth of the guiding cannula (103; FIG. 1). For example,the depth adjustment mechanism (104; FIG. 4A) may be adjusted such thata particular horizontal mark (145; FIG. 4A) lines up with the horizontalreference mark (172) such that a surgeon knows the exact insertion depthof the guiding cannula (103; FIG. 1). In some alternative embodiments,the retaining rail (108) only includes the straight pin (170). In theseembodiments, the straight pin (170) may include the horizontal referencemark (172).

FIG. 8 is a top view of an exemplary longitude adjustment plate (105).As shown in FIG. 8, the longitude adjustment plate (105) is in the shapeof a cylindrical ring and is configured to rotate about a centralvertical axis (181). As will be described in more detail below, thelongitude adjustment plate (105) includes a notch (180) that may bealigned with one of the marks (156; FIG. 5B) on the top surface of thecylindrical ring portion (155; FIG. 5B) of the main base (101; FIG. 5B)to adjust the longitudinal angle of the guiding cannula (103; FIG. 1).

Returning to FIG. 1, it can be seen that the longitude adjustment plate(105) is coupled to the retaining rail (108). The retaining rail (108),in turn, is coupled to the guiding plate (107). The guiding plate (107),in turn, is coupled to the proximal end portion (121; FIG. 2) of theguiding cannula (103). Hence, a rotation of the longitude adjustmentplate (105) shown in FIG. 8 about the central vertical axis (181)rotates the guiding cannula (103; FIG. 1) about the same centralvertical axis (181). In this manner, the longitudinal angle, θ, of thedistal tip (123; FIG. 1) of the guiding cannula (103; FIG. 1), asdescribed above in connection with FIGS. 3A-3B, may be adjusted to beequal to any angle between zero and 360 degrees. The longitudinallocking mechanism (106; FIG. 1) may be tightened to prevent thelongitude adjustment plate (105) from rotating about its centralvertical axis (181), thus locking the longitudinal angle of the distaltip (123; FIG. 1) of the guiding cannula (103; FIG. 1) in place. When itis desired to adjust the longitudinal angle, the longitudinal lockingmechanism (106; FIG. 1) is loosened and the longitude adjustment plate(105) is rotated until the notch (180) is aligned with the desiredlongitudinal angle as indicated by the marks (156; FIG. 5B) on the topsurface of the cylindrical ring portion (155; FIG. 5B) of the main base(101; FIG. 5B).

The longitude adjustment plate (105) of FIG. 8 is merely illustrative ofthe many devices that may be used to adjust the longitudinal angle ofthe guiding cannula (103; FIG. 1). Alternative longitudinal angleadjustment devices that may be used to adjust the longitudinal angle ofthe guiding cannula (103; FIG. 1) include, for example, a computerizedmotor or the like configured to adjust the longitudinal angle of theguiding cannula (103; FIG. 1).

By way of example, a method of locating an optimal site within the brainof a patient for deep brain stimulation will be described in connectionwith the flow chart of FIG. 9 and the illustrations FIGS. 10A-10G andmay be carried out according to the following sequence of procedures.The steps listed below may be modified, removed, reordered, and/or addedto as best serves a particular application.

1. A hole is drilled through the skull of a patient (step 210; FIG. 9).FIG. 10A illustrates an exemplary hole (190) that may be drilled throughthe skull (115). The hole (190) may be of a suitable size such that themain cannula (102; FIG. 1) may be inserted through the hole (190) andinto the brain of the patient. For example, the hole (190) may besubstantially equal to or less than eight millimeters in diameter. Thehole (190) may be secured by a burr hole plug shell, as shown.

2. The main base (101; FIG. 10A) and corresponding components aremounted on a stereotactic frame (109) (step 211; FIG. 9). As shown inFIG. 10A, the main base (101), longitude adjustment plate (105),longitudinal locking mechanism (106), and retaining rail (108) aremounted on the stereotactic frame (109) using any suitable mountingdevice (191). FIG. 10A shows that main base (101) and related componentsare positioned directly above the hole (190) such that the main cannula(102; FIG. 1) may be inserted into the hole (190).

3. A lead support base (193; FIG. 10B) is coupled to the main base (101)(step 212; FIG. 9). The lead support base (193) may be any structureconfigured to support a DBS lead as it is being inserted into the brain.A main cannula anchor device (192) may also be coupled to the main base(101). The main cannula anchor device (192) is configured to lock themain cannula (102; FIG. 1) into place once the main cannula (102;FIG. 1) has been inserted into the brain.

4. The main cannula (102; FIG. 10C) is inserted into the brain (step213; FIG. 9). As shown in FIG. 10C, the main cannula (102) and a stylet(194) are passed through the lumen of the main base (101) and insertedinto the brain. The stylet (194) is configured to precisely fill thelumen of the main cannula (102) to prevent coring of tissue whilecreating an entry path into the brain. The main cannula (102), withstylet (104) inserted, is advanced into the brain to a desired distanceabove a target site for microelectrode recording. For example, the maincannula (102) may be advanced into the brain to a distance substantiallyequal to 20 mm above the target site for microelectrode recording. Oncethe main cannula (102) is appropriately positioned, the main cannula(102) is clamped into place with the main cannula anchor device (192)and the stylet (194) is removed. If needed, a spacer cannula may firstbe inserted into the lumen of the main cannula (102).

5. As shown in FIGS. 10D and 10E, the guiding cannula (103), also knownas the microstimulator-guiding cannula, is then passed through the lumenof the depth adjustment mechanism (104), through the lumen of the maincannula (102), and into the brain (step 214; FIG. 9). A stylet mayalternatively be used to assist in the placement of the guiding cannula(103) into the brain. The guiding cannula (103) may be coupled to theguiding plate (107) using a securing nut (196). FIG. 10E shows that theguiding plate (107) includes a guiding tube (162) that slides onto thestraight pin (170) of the retaining rail (108).

The depth of the distal tip (123; FIG. 1) of the guiding cannula (103)may initially be set to be equal to the depth of the distal end of themain cannula (102). In some embodiments, the depth of the distal tip(123; FIG. 1) of the guiding cannula (103) is set to be equal to thedepth of the distal end of the main cannula (102) by rotating the depthadjustment mechanism (104) in a clockwise direction until a specifiedcircumferentially engraved marking on the depth adjustment mechanism(104) becomes aligned with a horizontal reference mark (172; FIG. 7)located on the wing member (171) of the retaining rail (108). The depthof the guiding cannula (103) may then be adjusted to any desired depthby further rotating the depth adjustment mechanism (104).

A desired longitudinal angle of the guiding cannula (103) may then beset, as illustrated in FIGS. 10F and 10G. The longitudinal lockingmechanism (106) is first loosened. The longitude adjustment plate (105)is then rotated to a desired longitudinal angle as indicated by themarks (156) on the cylindrical ring portion (155) of the main base(101). The longitudinal locking mechanism (106) is then tightened. FIG.10F shows the longitude adjustment plate (105) in a first position andFIG. 10G shows that the longitude adjustment plate (105) has beenrotated to a second position.

6. When the initially desired depth and longitudinal angle of theguiding cannula (103) have been set, the microelectrode (110) is passedthrough the lumen of the guiding cannula (103) and into the brain (step215; FIG. 9). The microelectrode (110) may be passed through the lumenof the guiding cannula (103) such that the distal tip (122; FIG. 1) ofthe microelectrode (110) protrudes a predetermined distance from thedistal tip (123; FIG. 1) of the guiding cannula (103) using anytechnique known in the art.

7. Microelectrode recording is then performed by the microelectrode(110) at a target site (step 216; FIG. 9).

8. The depth and longitudinal angle of the guiding cannula (103) may befurther adjusted such that the microelectrode (110) records or probes anumber of different target sites at varying depths and longitudinalangles until an optimal site within the brain for deep brain stimulationhas been located (steps 217, 218; FIG. 9). In some embodiments, the stepof adjusting the depth and longitudinal angle of the guiding cannula(103) may include one or more of the following sub-steps. First, themicroelectrode (110) is removed from the guiding cannula (103). Theguiding cannula (103) is adjusted such that the depth of the distal tip(123; FIG. 1) of the guiding cannula (103) is once again equal to orless than the depth of the distal end of the main cannula (102). Thelongitudinal angle is then adjusted to the new desired longitudinalangle. The depth of the guiding cannula (103) may then be adjusted tothe new desired depth. The microelectrode (110) may then be reinsertedinto the guiding cannula (103) and record or probe the new target site.

9. When an optimal site within the brain for deep brain stimulation hasbeen located by the microelectrode recording process (YES; step 217),the exact coordinates of the optimal site are calculated using theequations given above (step 219; FIG. 9). These exact coordinates may besubsequently used to insert a macroelectrode and/or DBS lead into thebrain at the optimal site as determined by the microelectrode recording.

10. The microelectrode (110) and guiding cannula (103) are removed fromthe DBS lead insertion system (100; FIG. 1) (step 220; FIG. 9). The maincannula (102) remains inserted into the brain.

11. A macroelectrode or a second guiding cannula (also known as amacroelectrode-guiding cannula) containing the macroelectrode may thenbe passed through the lumen of the main cannula (102) and into the brain(step 221; FIG. 9) such that the macroelectrode performsmacrostimulation at the optimal site for deep brain stimulation asdetermined previously by the microelectrode (110) probing (step 222;FIG. 9). The microstimulator-guiding cannula may have a bent distal endportion similar to the bent distal end portion (120; FIG. 2) of themicrostimulator-guiding cannula (103).

12. The macroelectrode is removed from the lumen of the main cannula(102; FIG. 1) (step 223; FIG. 9).

13. A DBS lead and/or catheter may be inserted into the brain via thelumen of the main cannula (102) (step 224; FIG. 9). The second guidingcannula (also known as the macrostimulator-guiding cannula) described inconnection with step 11 above or a third guiding cannula (also known asa lead-guiding cannula) may be used in some embodiments to facilitatethe insertion of the DBS lead and/or catheter into the brain.

14. Deep brain stimulation is applied to the optimal site within thebrain for deep brain stimulation via the DBS lead and/or catheter (step225; FIG. 9).

The preceding description has been presented only to illustrate anddescribe embodiments of the invention. It is not intended to beexhaustive or to limit the invention to any precise form disclosed. Manymodifications and variations are possible in light of the aboveteaching.

1. A method of locating an optimal site within a brain of a patient fordeep brain stimulation, said method comprising: inserting a distalportion of a main cannula into said brain, said main cannula having alumen; positioning a guiding cannula in said lumen of said main cannula,said guiding cannula comprising a lumen and a bent distal end portion;passing a microelectrode through said lumen of said guiding cannula intosaid brain; adjusting an insertion depth of said guiding cannula with adepth adjustment mechanism and a longitudinal angle of said guidingcannula with a longitudinal angle adjustment device such that saidmicroelectrode locates said optimal site for said deep brainstimulation; and passing a distal end of a macroelectrode or a deepbrain stimulation lead through said lumen of said main cannula and intosaid brain at said optimal site.
 2. The method of claim 1, wherein saidstep of adjusting said longitudinal angle of said guiding cannulacomprises rotating said longitudinal angle adjustment device about acentral vertical axis of said longitudinal angle adjustment device. 3.The method of claim 1, further comprising preventing operation of saidlongitudinal angle adjustment device.
 4. The method of claim 1, whereinsaid step of adjusting said insertion depth further comprises rotatingsaid depth adjustment mechanism about a central vertical axis of saiddepth adjustment mechanism.
 5. The method of claim 1, wherein said depthadjustment mechanism comprises a number of marks, wherein each of saidmarks corresponds to a particular insertion depth of said guidingcannula.
 6. The method of claim 1, further comprising: calculating anumber of coordinates corresponding to said optimal site; andpositioning said distal end of said macroelectrode or said distal end ofsaid deep brain stimulation lead according to said coordinates.
 7. Themethod of claim 6, wherein said step of calculating said number ofcoordinates further comprises calculating said coordinates withreference to a location corresponding to a distal end of said maincannula.
 8. The method of claim 1, further comprising calculating alocation of said optimal site according to the following equation, saidlocation represented by B_((x,y,z)):B _((x,y,z)) =B _((a·cos θ,a·sin θ,r·sin(360h/πr) ₂ _()+AB·cos(360h/πr)₂ ₎₎; wherein x is a first dimensional coordinate substantially equal toa·cos θ, y is a second dimensional coordinate substantially equal toa·sin θ, and z is a third dimensional coordinate substantially equal tor·sin(360h/πr²)+AB·cos(360h/πr²); wherein r represents a radius of saidbent distal end portion of said guiding cannula, θ represents saidlongitudinal angle, h represents a maximum possible insertion depth of adistal tip of said guiding cannula, and AB+h represents a maximumpossible insertion depth of a tip of said microelectrode.
 9. The methodof claim 8, further comprising positioning said distal end of saidmacroelectrode or said distal end of said deep brain stimulation lead atsaid location of said optimal site.
 10. A method of locating an optimalsite within a brain of a patient for deep brain stimulation, said methodcomprising: passing a microelectrode through a lumen of a guidingcannula and into said brain, said guiding cannula having a bent distalend portion; adjusting an insertion depth of said microelectrode withinsaid brain; and adjusting a longitudinal angle of said microelectrode.11. The method of claim 10, further comprising: calculating a number ofcoordinates corresponding to said optimal site.
 12. The method of claim10, further comprising calculating said coordinates of said optimal siteaccording to the following equation, said location represented byB_((x,y,z)):B _((x,y,z)) =B _((a·cos θ,a·sin θ,r·sin(360h/πr) ₂ _()+AB·cos(360h/πr)₂ ₎₎; wherein x is a first dimensional coordinate substantially equal toa·cos θ, y is a second dimensional coordinate substantially equal toa·sin θ, and z is a third dimensional coordinate substantially equal tor·sin(360h/πr²)+AB·cos(360h/πr²); wherein r represents a radius of saidbent distal end portion of said guiding cannula, θ represents saidlongitudinal angle, h represents a maximum possible insertion depth of adistal tip of said guiding cannula, and AB+h represents a maximumpossible insertion depth of a tip of said microelectrode.
 13. The methodof claim 12, further comprising positioning a distal end of amacroelectrode or a distal end of a deep brain stimulation lead at saidcoordinates of said optimal site.
 14. The method of claim 10, whereinsaid step of adjusting said insertion depth of said microelectrodewithin said brain comprises adjusting an insertion depth of said guidingcannula.
 15. The method of claim 10, wherein said step of adjusting saidlongitudinal angle of the microelectrode comprises adjusting alongitudinal angle of said guiding cannula.
 16. A method of locating anoptimal site for deep brain stimulation, said method comprising: (a)inserting a portion of a main cannula into said brain, said main cannulahaving a lumen; (b) inserting a portion of a guiding cannula into saidlumen of said main cannula, said guiding cannula having a lumen and abent distal end portion; (c) adjusting a longitudinal angle of saidguiding cannula; (d) adjusting an insertion depth of said guidingcannula while introducing a distal portion of said guiding cannula intosaid brain; (e) passing a microelectrode through said lumen of saidguiding cannula into said brain such that said microelectrode locatessaid optimal site for deep brain stimulation (DBS); and (f) wherein ifan optimal stimulation site is not located by said microelectrode, saidmethod comprises retracting said microelectrode and said guiding cannulaout of said brain and repeating steps (c), (d), (e) and (f).
 17. Themethod of claim 16, further comprising calculating a location of saidoptimal stimulation site.
 18. The method of claim 17, wherein said stepof calculating said location of said optimal stimulation site comprisescalculating coordinates of said optimal site according to the followingequation, said location represented by B_((x,y,z)):B _((x,y,z)) =B _((a·cos θ,a·sin θ,r·sin(360h/πr) ₂ _()+AB·cos(360h/πr)₂ ₎₎; wherein x is a first dimensional coordinate substantially equal toa·cos θ, y is a second dimensional coordinate substantially equal toa·sin θ, and z is a third dimensional coordinate substantially equal tor·sin(360h/πr²)+AB·cos(360h/πr²); wherein r represents a radius of saidbent distal end portion of said guiding cannula, θ represents saidlongitudinal angle, h represents a maximum possible insertion depth of adistal tip of said guiding cannula, and AB+h represents a maximumpossible insertion depth of a tip of said microelectrode.
 19. The methodof claim 17, further comprising removing said microelectrode andinserting a macroelectrode or DBS lead such that a distal tip of saidmacroelectrode or DBS lead is positioned at said calculated optimalstimulation site.
 20. The method of claim 16, further comprisingadjusting said longitudinal angle of said guiding cannula with alongitudinal angle adjustment device by rotating said longitudinal angleadjustment device about a central vertical axis of said longitudinalangle adjustment device.